Chronic obstructive pulmonary disease (COPD) is a term that encompasses a group of chronic lung conditions characterized by obstruction of the airways of the lungs. COPD generally includes two major breathing diseases: chronic (obstructive) bronchitis and emphysema. Both breathing diseases make breathing difficult and cause breathlessness. COPD may be, but not necessarily, accompanied by primary pulmonary hypertension (PPH) or secondary pulmonary hypertension (SPH).
Chronic bronchitis is an progressive inflammatory disease that begins in the smaller airways within the lungs and gradually advances to larger airways. It increases mucous production in the airways and increases the occurrence of bacterial infection in the bronchial tree, which, in turn, impedes airflow. This chronic inflammation induces thickening of the walls of the bronchial tree leading to increased congestion in the lungs, which results in dyspnea. By definition, chronic bronchitis, refers to a productive cough for at least three months of each of two successive years for which other causes have been ruled out.
Emphysema comprises COPD that damages and destroys lung architecture with enlargement of the airspaces and loss of alveolar surface area. Lung damage is caused by weakening and breaking of air sacks, i.e., alveoli, within the lungs. Several adjacent alveoli may rupture, forming one large space instead of many small ones. Larger spaces can combine into an even bigger cavity, called a bulla. As a result, natural elasticity of the lung tissue is lost, leading to overstretching and rupture. There also is less pull on the smaller bronchial tubes, which can cause them to collapse and thus obstruct airflow. Air that is not exhaled before new air is inhaled gets trapped in the lungs, leading to shortness of breath. The sheer effort it takes a person suffering from emphysema to force air out of the lungs when exhaling can be exhausting.
COPD is always accompanied by bronchial obstruction. Thus, the most common symptoms of COPD include, shortness of breath, chronic coughing, chest tightness, greater effort to breathe, increased mucous production and frequent clearing of the throat. Patients are often unable to perform their daily activities. Independent development of chronic bronchitis and emphysema is possible, but most people with COPD have a combination of the two disorders. Both conditions decrease the ability of the lungs to take in oxygen and remove carbon dioxide.
Tuberculosis is another important lung disease. Tuberculosis most commonly attacks the lungs, but can also affect the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, bones, joints and even the skin. Several Mycobacteria such as Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti can also cause tuberculosis. Symptoms of tuberculosis include a severe cough that lasts, weight loss, coughing up blood or mucus, weakness or fatigue, fever and chills, night sweats, loss of appetite.
Lung cancer is a particularly deadly lung disease. Typically, treatment of lung cancer includes systematic administration of chemotherapeutic agents, e.g., cytotoxic agents, to patients. Often such administration is associated with adverse side effects including nephrotoxicity and bone marrow toxicity. The nephrotoxicity limits the frequency at which clinicians can administer antitumor agents to patients. The prolonged time periods for systematic administration of antitumor agents leads to increased patient discomfort and inconvenience which may lead to decreased patient compliance.
Inhalation therapies may be attractive alternatives to some lung diseases because of reduced cost. However, current inhalation therapies have significant disadvantages which have limited their use in this area such as: no enhanced targeting to diseased cells, no protection from in vivo degradation in the lungs and short term therapeutic effects due to rapid clearance of the drug from the lung, requiring frequent administration of the drug.
What is needed is a method of targeting sustained release formulations of therapeutic agents for treating lung diseases. The current invention provides such methods.